Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1
Kristin L Granlund, Sui-Seng Tee, Hebert A Vargas, Serge K Lyashchenko, Ed Reznik, Samson Fine, Vincent Laudone, James A Eastham, Karim A Touijer, Victor E Reuter, Mithat Gonen, Ramon E Sosa, Duane Nicholson, YanWei W Guo, Albert P Chen, James Tropp, Fraser Robb, Hedvig Hricak, Kayvan R Keshari, Kristin L Granlund, Sui-Seng Tee, Hebert A Vargas, Serge K Lyashchenko, Ed Reznik, Samson Fine, Vincent Laudone, James A Eastham, Karim A Touijer, Victor E Reuter, Mithat Gonen, Ramon E Sosa, Duane Nicholson, YanWei W Guo, Albert P Chen, James Tropp, Fraser Robb, Hedvig Hricak, Kayvan R Keshari
Abstract
Metabolic imaging using hyperpolarized magnetic resonance can increase the sensitivity of MRI, though its ability to inform on relevant changes to biochemistry in humans remains unclear. In this work, we image pyruvate metabolism in patients, assessing the reproducibility of delivery and conversion in the setting of primary prostate cancer. We show that the time to max of pyruvate does not vary significantly within patients undergoing two separate injections or across patients. Furthermore, we show that lactate increases with Gleason grade. RNA sequencing data demonstrate a significant increase in the predominant pyruvate uptake transporter, monocarboxylate transporter 1. Increased protein expression was also observed in regions of high lactate signal, implicating it as the driver of lactate signal in vivo. Targeted DNA sequencing for actionable mutations revealed the highest lactate occurred in patients with PTEN loss. This work identifies a potential link between actionable genomic alterations and metabolic information derived from hyperpolarized pyruvate MRI.
Trial registration: ClinicalTrials.gov NCT02421380.
Keywords: glycolytic flux; hyperpolarized pyruvate; in vivo kinetics; metabolic imaging.
Conflict of interest statement
Declaration of Interests: APC and FR are employed by General Electric Healthcare. JT is employed by Berkshire Magnetics. HH is on the board of IBA. KRK serves on the SAB of NVision Imaging Technologies.
Copyright © 2019 Elsevier Inc. All rights reserved.
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Source: PubMed